Lesions of the Suprachiasmatic Nucleus Eliminate the Daily Rhythm of Hypocretin-1 Release

• Published in: Sleep (New York, N.Y.) Vol. 27; no. 4; pp. 619 - 627
• Main Authors: Zhang, Shengwen, Zeitzer, Jamie M., Yoshida, Yasushi, Wisor, Jonathan P., Nishino, Seiji, Edgar, Dale M., Mignot, Emmanuel
• Format: Journal Article
• Language: English
• Published: Rochester, MN American Academy of Sleep Medicine 15.06.2004
• Subjects: Anatomical correlates of behavior; Animals; Behavioral psychophysiology; Biological and medical sciences; Body Temperature - physiology; Carrier Proteins - cerebrospinal fluid; Carrier Proteins - metabolism; Circadian Rhythm - physiology; Fundamental and applied biological sciences. Psychology; Intracellular Signaling Peptides and Proteins; Locomotion - physiology; Narcolepsy - cerebrospinal fluid; Narcolepsy - metabolism; Narcolepsy - pathology; Neuropeptides - cerebrospinal fluid; Neuropeptides - metabolism; Orexins; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Radioimmunoassay; Rats; Suprachiasmatic Nucleus - pathology; Suprachiasmatic nucleus; Animal model; Nervous system diseases; Rat; Rodentia; Central nervous system; Sleep disorder; Biological rhythm; Hypothalamus; Circadian rhythm; Encephalon; Locomotion; Vertebrata; Animal activity; Mammalia; Spontaneous physical activity; Animal; Narcolepsy; Lesion; Neurological disorder; Orexin
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleep/27.4.619

Hypocretins (orexins) are involved in the sleep disorder narcolepsy. While hypocretin-1 has a daily oscillation, little is known regarding the relative contribution of circadian and homeostatic components on hypocretin release. The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined. SCN-ablated (SCNx) and sham-operated control rats were implanted with activity-temperature transmitters. Animals were housed individually under 1 of 3 lighting conditions: 12-hour:12-hour light:dark cycle (LD), constant light (LL), and constant darkness (DD). Lesions were verified histologically and shown not to affect hypocretin-containing cells. Hypocretin-1 concentrations in the CSF were determined every 4 hours using radioimmunoassays. Control animals displayed robust circadian (LL, DD) and diurnal (LD) fluctuations in CSF hypocretin-1, locomotor activity, and temperature. Peak CSF hypocretin-1 was at the end of the active period. Activity, temperature, and CSF hypocretin-1 were arrhythmic in SCNx animals in LL and DD. In LD, a weak but significant fluctuation in activity and temperature but not CSF hypocretin-1 was observed in SCNx animals. We also explored correlations between CSF hypocretin-1, CSF corticosterone, and locomotor activity occurring prior to CSF sampling in arrhythmic SCNx rats under constant conditions. Significant correlations between hypocretin-1 and activity were observed both across and within animals, suggesting that interindividual and time-of-the-day differences in activity have significant effects on hypocretin release in arrhythmic animals. No correlation was found between CSF hypocretin-1 and corticosterone. Hypocretin-1 release is under SCN control. Locomotor activity influences the activity of the hypocretin neurons.